Fruit Flies on Cocaine Could Reveal Better Therapies for Addiction
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For the first time, researchers have created genetically modified fruit flies that can become addicted to cocaine. The flies will self-administer cocaine if given the option. The new model could prove immensely valuable for the development of new therapies to prevent and treat cocaine use disorder, a growing and deadly concern that affects about 1.5 million people nationwide.
Heredity strongly impacts the risk of developing cocaine use disorder, but the large number of genes implicated in addiction risk has made it difficult to determine which might be the best targets for therapeutics.
With their new fruit fly model of cocaine use disorder, the researchers hope to reveal the biology of addiction and find better therapies much faster than was previously possible.
Key points:
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Researchers have created fruit flies that can become addicted to cocaine.
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The flies will self-administer cocaine if given the option.
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Flies and humans react to cocaine in similar ways, and are likely to share many of the genes that affect addiction risk.
IMPACT: The new model will help scientists rapidly reveal the biology of addiction and develop better therapies for cocaine use disorder, which affects 1.5 million Americans.
High-flying aspirations
Flies and humans react to cocaine in remarkably similar ways, says associate professor of psychiatry at the University of Utah and the senior author on the study. 鈥淎t low doses, they start running around, just like people,鈥 Rothenfluh says. 鈥淎t very high doses, they get incapacitated, which is also true in people.鈥
Flies and humans have a lot in common when it comes to addiction. Flies have about 75% of the human genes that are known to be involved in disease, and the insects have been instrumental in discovering the underlying biology behind other substance dependencies.
Because fruit flies grow quickly and are easy to conduct genetic experiments with, a fruit fly model of cocaine use disorder would be a valuable early step toward developing therapies.
There is just one problem鈥攐ne very significant difference between flies and humans鈥擱othenfluh says: 鈥淔lies do not like cocaine one bit.鈥
His research team found that when given a choice between sugar water and sugar water laced with cocaine, fruit flies consistently chose the drug-free option, even when they鈥檇 been exposed to cocaine previously. To better understand addiction in humans, the scientists needed to figure out why flies wouldn鈥檛 take cocaine鈥攁nd if there was a way to bypass that barrier.
The bitter truth
first author on the paper, suspected that the answer might lie in the flies鈥 sense of taste.
鈥淚nsects are evolutionarily primed to avoid plant toxins, and cocaine is a plant toxin,鈥 says Philyaw, now a research scientist at University of Washington, who did the research as a graduate student in Rothenfluh鈥檚 lab. 鈥淭hey have taste receptors on their 鈥榓rms鈥欌攖heir tarsal segments鈥攕o they can put their hand in something before it goes in their mouth, and decide, 鈥業鈥檓 not going to touch that.鈥欌
By watching how flies鈥 sensory nerves responded to cocaine, the researchers found that the compound strongly activates bitter-sensing taste receptors in the flies鈥 tarsal segments.
When the researchers muted the activity of those bitter-sensing nerves so that the flies couldn鈥檛 taste bitter flavors, they did start developing a preference for cocaine-laced sugar water over plain sugar water. The dosage was important鈥攆lies would only voluntarily consume cocaine at low concentrations鈥攂ut they developed a preference remarkably quickly, within 16 hours of first exposure.
From insects to impacts
The researchers say this will help them understand addiction in humans. Now that scientists can study the process in fruit flies, the pipeline to new discoveries can be greatly accelerated, studying hundreds of potentially relevant genes in a much shorter time span.
鈥淲e can scale research so quickly in flies,鈥 Philyaw says. 鈥淲e can identify risk genes that might be difficult to uncover in more complex organisms, and then we pass that information to researchers who work with mammalian models. Then, they鈥檙e able to uncover treatment targets that facilitate the jump from studying animal behavior to developing human therapeutics.鈥
Rothenfluh agrees: 鈥淲e can really start to understand the mechanisms of cocaine choice, and the more you understand about the mechanism, the more you have a chance to find a therapeutic that might act on that mechanism.鈥
In addition to specific searches for therapeutics, Rothenfluh says basic research into the mechanisms of how the human mind鈥攁nd the fruit fly mind鈥攚ork can have unexpected impacts. 鈥淛ust trying to understand the simple little fly brain can give us insights that you cannot anticipate,鈥 he emphasizes. 鈥淏asic science is important, and you never know what exciting things you might find that turn out to be impactful for understanding the human condition.鈥
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This research is published in Journal of Neuroscience as
The work was funded by the Huntsman Mental Health Institute, the University of Utah Molecular Medicine Program, and the National Institutes of Health, including the National Institute of Diabetes and Digestive and Kidney Diseases (grant number R01DK110358), the National Institute on Drug Abuse (grants K01DA058919, R21DA049635, and R21DA040439), and the National Institute on Alcohol Abuse and Alcoholism (grants R01AA026818, R01AA019536-S1, and R01AA030881). Content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.